rs1476991

Variant names:

• chr7-29480426-G-A
• rs1476991
• NM_004067.4:c.654+70G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-29480426-G-A
• chr7-29480426-G-C
• chr7-29480426-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004067.4(CHN2):​c.654+70G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 1,483,598 control chromosomes in the GnomAD database, including 112,307 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.33 (8860 hom., cov: 33)
  • Exomes 𝑓: 0.39 (103447 hom.)
• Consequence: CHN2 NM_004067.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93
• Publications: 11 publications found

Genes affected

CHN2 (HGNC:1944): (chimerin 2) This gene encodes a guanosine triphosphate (GTP)-metabolizing protein that contains a phorbol-ester/diacylglycerol (DAG)-type zinc finger, a Rho-GAP domain, and an SH2 domain. The encoded protein translocates from the cytosol to the Golgi apparatus membrane upon binding by diacylglycerol (DAG). Activity of this protein is important in cell proliferation and migration, and expression changes in this gene have been detected in cancers. A mutation in this gene has also been associated with schizophrenia in men. Alternative transcript splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, May 2014]

PRR15-DT (HGNC:55866): (PRR15 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004067.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHN2	NM_004067.4	MANE Select	c.654+70G>A		intron	N/A	NP_004058.1	P52757-1
	CHN2	NM_001293070.2		c.693+70G>A		intron	N/A	NP_001279999.1	B7Z1V0
	CHN2	NM_001293072.2		c.609+70G>A		intron	N/A	NP_001280001.1	B7Z1W9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHN2	ENST00000222792.11	TSL:1 MANE Select	c.654+70G>A		intron	N/A	ENSP00000222792.7	P52757-1
	CHN2	ENST00000421775.6	TSL:1	c.246+70G>A		intron	N/A	ENSP00000394284.2	P52757-5
	CHN2	ENST00000409041.8	TSL:1	c.246+70G>A		intron	N/A	ENSP00000386849.5	B3VCF5

Frequencies

GnomAD3 genomes AF: 0.329 AC: 50065 AN: 152048 Hom.: 8862 Cov.: 33

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.337

GnomAD4 exome AF: 0.392 AC: 521620 AN: 1331432 Hom.: 103447 AF XY: 0.394 AC XY: 262736 AN XY: 666560

African (AFR) AF: 0.183 AC: 5571 AN: 30370

American (AMR) AF: 0.314 AC: 13400 AN: 42618

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 9970 AN: 24732

East Asian (EAS) AF: 0.415 AC: 16101 AN: 38836

South Asian (SAS) AF: 0.442 AC: 36221 AN: 81860

European-Finnish (FIN) AF: 0.352 AC: 18588 AN: 52850

Middle Eastern (MID) AF: 0.370 AC: 2028 AN: 5482

European-Non Finnish (NFE) AF: 0.399 AC: 398461 AN: 998804

Other (OTH) AF: 0.381 AC: 21280 AN: 55880

GnomAD4 genome AF: 0.329 AC: 50064 AN: 152166 Hom.: 8860 Cov.: 33 AF XY: 0.329 AC XY: 24438 AN XY: 74390

African (AFR) AF: 0.186 AC: 7742 AN: 41528

American (AMR) AF: 0.347 AC: 5313 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1330 AN: 3470

East Asian (EAS) AF: 0.407 AC: 2100 AN: 5166

South Asian (SAS) AF: 0.435 AC: 2097 AN: 4826

European-Finnish (FIN) AF: 0.342 AC: 3624 AN: 10584

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.396 AC: 26900 AN: 67976

Other (OTH) AF: 0.335 AC: 707 AN: 2110

Alfa AF: 0.373 Hom.: 18917

Bravo AF: 0.321

Asia WGS AF: 0.378 AC: 1312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.020
DANN	Benign	0.39
PhyloP100		-1.9
PromoterAI		-0.063	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1476991; hg19: chr7-29520042;